IMPORTANCE Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. OBJECTIVE To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. INTERVENTIONS Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of tracheal intubation or mortality within 30 days. RESULTSThe trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, −8% [95% CI, −15% to −1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, −1% [95% CI, −8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings.

The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.

Background Both continuous positive airway pressure (CPAP) and high-flow nasal oxygenation (HFNO) have been recommended for acute respiratory failure in COVID-19. However, uncertainty exists regarding effectiveness and safety. Methods In the Recovery- Respiratory Support multi-center, three-arm, open-label, adaptive, randomized controlled trial, adult hospitalized patients with acute respiratory failure due to COVID-19, deemed suitable for treatment escalation, were randomly assigned to receive CPAP, HFNO, or conventional oxygen therapy. Comparisons were made between each intervention and conventional oxygen therapy. The primary outcome was a composite of tracheal intubation or mortality within 30-days. Results Over 13-months, 1272 participants were randomized and included in the analysis (380 (29.9%) CPAP; 417 (32.8%) HFNO; 475 (37.3%) conventional oxygen therapy). The need for tracheal intubation or mortality within 30-days was lower in the CPAP group (CPAP 137 of 377 participants (36.3%) vs conventional oxygen therapy 158 of 356 participants (44.4%); unadjusted odds ratio 0.72; 95% CI 0.53 to 0.96, P=0.03). There was no difference between HFNO and conventional oxygen therapy (HFNO 184 of 414 participants (44.4%) vs conventional oxygen therapy 166 of 368 participants (45.1%); unadjusted odds ratio 0.97; 95% CI 0.73 to 1.29, P=0.85). Conclusions CPAP, compared with conventional oxygen therapy, reduced the composite outcome of intubation or death within 30 days of randomisation in hospitalized adults with acute respiratory failure due to COVID-19. There was no effect observed, compared with conventional oxygen therapy, with the use of HFNO. (Funded by the UK National Institute for Health Research; ISRCTN 16912075).

1 This study investigates the effects of androgens, the antiandrogen flutamide and green tea catechins on glucose transport inhibition in human erythrocytes. These effects may relate to the antidiabetogenic effects of green tea. 2 Testosterone, 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA) and DHEA-3-acetate inhibit glucose exit from human erythrocytes with half-maximal inhibitions (K i ) of 39.278.9, 29.673.7, 48.1710.2 and 4.870.98 mM, respectively. The antiandrogen flutamide competitively relieves these inhibitions and of phloretin. Dehydrotestosterone has no effect on glucose transport, indicating the differences between androgen interaction with GLUT1 and human androgen receptor (hAR). 3 Green tea catechins also inhibit glucose exit from erythrocytes. Epicatechin 3-gallate (ECG) has a K i ECG of 0.1470.01 mM, and epigallocatechin 3-gallate (EGCG) has a K i EGCG of 0.9770.13 mM. Flutamide reverses these effects. 4 Androgen-screening tests show that the green tea catechins do not act genomically. The high affinities of ECG and EGCG for GLUT1 indicate that this might be their physiological site of action. 5 There are sequence homologies between GLUT1 and the ligand-binding domain (LBD) of hAR containing the amino-acid triads Arg 126, Thr 30 and Asn 288, and Arg 126, Thr 30 and Asn 29, with similar 3D topology to the polar groups binding 3-keto and 17-b OH steroid groups in hAR LBD. These triads are appropriately sited for competitive inhibition of glucose import at the external opening of the hydrophilic pore traversing GLUT1.

Small intramural fibroids are associated with a significant reduction in the cumulative pregnancy, ongoing pregnancy and live birth rates after three IVF/ICSI cycles.

Xpert MTB/RIF provides a rapid, useful, and accurate test to diagnose mediastinal nodal TB in intermediate-incidence settings. The additional use of TBNA cytology further enhances the sensitivity of Xpert. This combination can facilitate rapid risk assessment and prompt TB treatment.

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A 22-year-old man presented with recurrent palpable purpuric rash. His clubbing relates to underlying cystic fibrosis (CF) and his rash was identified as CF-related vasculitis, a rare extrapulmonary manifestation of the disease. It occurs predominantly on the lower limbs, mainly over the dorsa of the feet, ankles and tibial surfaces. The rash occurred while the patient had an infective exacerbation of CF (IECF), however, there had also been previous occurrences without worsening of his pulmonary symptoms, to which the rash remitted spontaneously. The patient responded well to immunosuppression, which was given on this admission due to worsening of his CF-related vasculitis. He died 18 months within the onset of his initial rash.